Relaxin was originally discovered as a hormone of pregnancy; promoting cardiovascular and renal adjustments to meet the increased nutritional demands of the growing fetus, the elevated requirements for renal clearance of metabolic wastes, and the relaxation of smooth muscle and ligaments to facilitate labor and delivery. The relaxin/insulin-like family peptide receptor 1 (RXFP1) has both antifibrotic and vasodilatory effects when stimulated by relaxin. While recombinant relaxin has been explored clinically for various diseases, its short half-life and requirement for intravenous delivery present obstacles for longer-term use. To circumvent these limitations, the lead collaborators have identified a synthetic small molecule agonist of RXFP1 (ML290) as an alternative to relaxin hormone. In an animal model of chemically-induced fibrosis, ML290 was shown to reverse fibrotic damage. In a second animal model of hypoxia-conditioned PAH, ML290 was shown to reduce right ventricular systolic pressure and attenuate right ventricular hypertrophy after intraperitoneal administration. These observations support the hypothesis that ML290 could be useful to treat PAH in patients with idiopathic pulmonary fibrosis. TRND scientists have initiated a medicinal chemistry campaign to optimize ML290, with the goal of developing a new lead that is active in the mouse after oral administration.